Funds are requested for a 3-channel transcranial magnetic stimulation (TMS) system with simultaneous whole-head 64-channel electroencephalography (EEG) instrument. The fully integrated instrument system includes a magnetic resonance imaging (MRI) guided frameless stereotactic navigator, coupled with three powerful stimulators and small but efficient cooled TMS coils that allow spatiotemporally precise injection of current into up to 3 brain areas. Multi- channel TMS is of key value because even simple stimuli and tasks involve networks that engage multiple distinct brain regions (nodes). Thus, in order to probe and modulate network properties of the human brain, single-channel TMS systems (one stimulator, one coil) that target one node of a network are often not sufficient. Multi-channel arrangements (multiple stimulators, each with one coil) can modulate multiple nodes - even different nodes into different directions - and therefore offer much greater control over networks, permitting development of novel diagnostic and therapeutic brain stimulation/modulation regimens. The temporal relations between the three stimulation targets can be adjusted to achieve different types of effects. For example, network state and functional organization can be probed by delivering the TMS pulses in rapid millisecond-level biologically inspired sequences. With paired-pulse TMS techniques, each of the targeted cortical areas can be switched ON or OFF for a short time (~tens of milliseconds). Further, repetitive TMS of multiple sites can be used to change the functional connectivity between them using Hebbian principles, which can be experimentally and therapeutically valuable. All of the above TMS techniques can be used for non-invasive validation of models based on neuroimaging (fMRI/PET/EEG/MEG) data. To understand how brain functions change as a result of TMS we will use simultaneous TMS+EEG and/or TMS+fMRI. These techniques are also used to probe cortical excitability, functional state, and interregional connectivity. The instrument system thus allows noninvasive network-level modulation of the human brain, as is necessary to test for causal roles of brain regions and networks in healthy individuals. These methods could be ultimately used to induce plastic changes to steer networks away from pathological states associated with neurological and psychiatric disorders. The instrument components are selected to allow multi-channel MRI- guided TMS and simultaneous TMS+EEG and TMS+fMRI in an integrated instrument system. The instrument will be situated at the Rehabilitation Institute of Chicago (RIC), a leading neurological rehabilitation and research hospital worldwide. The instrument will support a large number of NIH funded large-scale grants (N=26) and PIs (N=20) from several Chicago area institutions (RIC, Northwestern University, and University of Illinois at Chicago) and is likely to become a widely used research resource in the Midwestern US. The Advisory Committee has hands-on expertise in building and managing multi-channel TMS/imaging instruments and the RIC institutional support is strong.